TFLLR-NH2-TFA _Protease-Activated Receptor (PAR) Agonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETFLLR-NH2(TFA)Cat. No.: HY-P0226ACAS No.: 1313730-19-6分式: CHFNO分量: 761.83Sequence: Thr-Phe-Leu-Leu-Arg-NH2Sequence Shortening: TFLLR-NH2作靶點(diǎn): Protease-Activated Receptor (PAR)作通路: GPCR/G Protein儲(chǔ)存式: Powder -80C 2 years-20C 1 year

2、In solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (131.26 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.3126 mL 6.5631 mL 13.1263 mL5 mM 0.2625 mL 1.3126 mL 2.6253 mL10 mM 0.1313 mL 0.6563 mL 1.3126 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給

3、藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.28 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑

4、師www.MedChemESolubility: 2.5 mg/mL (3.28 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.28 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TFLLR-NH2 (TFA)是選擇性的 PAR1 激動(dòng)劑，EC50 值為 1.9 M。IC50 & Target EC50: 1.9 M (PAR1) 1體外研究 PAR1 agonists stimulate concentration-dependent incr

5、eases in Ca2+i and in the proportions of neurones.The maximal increase in Ca2+i above basal is detected in response to 10m TF-NH2 (peak 196.520.4nM, n=25) when 5080% of identified neurones responded 1. SW620 cells cultured in the supernatant ofTFLLR-NH2-activated platelets upregulate E-cadherin expr

6、ession and downregulate the vimentin expression.In the in vitro platelet culture system, a TFLLR-NH2 dose-dependent increase of secreted TGF-1 isdetected in the supernatant 2.體內(nèi)研究 Injection of TF-NH2 into the rat paw stimulates a marked and sustained oedema. An NK1R antagonist andablation of sensory

7、 nerves with capsaicin inhibit oedema by 44% at 1h and completely by 5h. In wild-typebut not PAR1/ mice, TF-NH2 stimulates Evans blue extravasation in the bladder, oesophagus, stomach,intestine and pancreas by 28 fold. Extravasation in the bladder, oesophagus and stomach is abolished byan NK1R antag

8、onist 1. TFp-NH2 produces notable contraction at 3-50 M and relaxation at 0.3-50 M, inthe absence of apamin. The concentration-response curve for TFp-NH2-induced contraction is remarkablyshifted left, when the TFp-NH2-induced relaxation is blocked by apamin at 0.1 M 3.PROTOCOLAnimal Mice 1Administra

9、tion 1 Mice are anaesthetized with isofluorane, and saline or TF-NH2 (3mol/kg in 25L physiological saline) isinjected into the lateral tail vein. Evans blue (33.3mg/kg in 50L saline) is co-injected with the peptide. Miceare perfused transcardially at 10min after administration of TF-NH2 with physiol

10、ogical saline containing 20u/mL heparin at a pressure of 80-100mmHg for 2-3min. Excised tissues are incubated in 1mL of formamidefor 48h, and Evans blue content is measured spectrophotometrically at 650nm 1.MCE has not independently confirmed the accuracy of these methods. They are for reference onl

11、y.REFERENCES1. de Garavilla L, et al. Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br JPharmacol. 2001 Aug;133(7):975-87.2. Kawabata A, et al. Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smoothmuscle.3. Jia Y, et al. Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEcancer cell line SW620. Oncol Rep. 2015 Jun;33(6):2681-8.McePdfHeightCaution: Pro